Lysosomal targeting bifunctional molecules for degradation of autoantibodies
AssigneeLycia Therapeutics, Inc.
InventorsDarrin Anthony Lindhout, Tao Chen, Richard Glynne, Jeffrey Iwig, Jason G. Lewis, Diana Li, Nicholas Lind, Matthew Shurtleff, Steven Staben, Sarah Michelle Totten, Eric D. Turtle
Life of this patent
Estimating the term…
Abstract
The present disclosure provides bifunctional molecules including a moiety that targets a lysosomal targeting molecule, a linker, and a polypeptide that specifically binds a extracellular target molecule such as an antibody that is targeted for degradation.
Claims39
An extracellular target binding conjugate of formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- X is a moiety that binds to a lysosomal targeting molecule;
- n is 1 to 50;
- L is a linker;
- m is the average number of (Xn-L) moieties conjugated to Y—B, wherein m is in the range from 1 to 20:
- Y is an optional carrier polypeptide connected to B;
- and
- B is a polypeptide that specifically binds an extracellular target molecule.
The conjugate of any preceding claim, wherein the conjugate is of formula (I′):
- or a prodrug thereof, or a or a pharmaceutically acceptable salt thereof,
- wherein:
- n is 1 to 500;
- m is 1 to 20;
- X is the ligand moiety;
- and
- Y is the target-binding moiety.
The conjugate of any preceding claim, wherein the lysosomal targeting molecule is a cell surface receptor that provides for internalization of the conjugate.
The conjugate of any preceding claim, wherein the lysosomal targeting molecule is selected from asialoglycoprotein receptor (ASGPR), cation independent mannose-6-phosphate receptor (CI-M6PR also referred to herein as M6PR), folate receptor, LDLR, CD63, sortilin, IFITM3, molecules in the endosome/lysosome pathway, LIMP-1, and LIMP-2.
The conjugate of any preceding claim, wherein X is a moiety that binds ASGPR or M6PR.
The conjugate of any preceding claim, wherein X is a moiety that binds ASGPR.
The conjugate of claim 34, wherein -L-Y comprises:
- wherein RY is
The conjugate of any preceding claim, wherein L comprises of 10 to 60 consecutive branched or linear chain atoms.
The conjugate of any preceding claim, wherein L is of formula (IIb′):
- wherein:
- n is 1, 2, or 3;
- each L1 to L6 is independently a linking moiety which together provide a linear or branched linker between Z1 and Y;
- a, b, c, d, and e are each independently 1, 2, 3, 4, or 5;
- ** represents the point of attachment to L1 of X via Z1;
- and
- *** represents the point of attachment to Y.
Dependencies are inferred from the claim text.